Our investigations continue to be sharply focused on determining the role of neural and psychologic factors in the precipitation of malignant ventricular arrhythmias which lead to sudden cardiac death. We have deemed these as transient risk factors which in the electrically unstable heart provoke repetitive ventricular arrhythmias culminating in ventricular fibrillation. Animal and human studies will concentrate on the following: 1) Explore the tonic vagal inputs on the heart and assess the extent to which these influence ventricular vulnerability in the conscious animal. 2) Determine the role of dopaminergic and serotonergic agonists on the susceptibility of the stressed animal to ventricular fibrillation. 3) Study the contribution of alpha-adrenergic receptors in affecting the vulnerable period threshold. 4) Investigate diurnal heart rate variation and how these predict the predisposition of animals to psychologic stress-induced myocardial electrophysiologic changes. 5) Finally we intend to develop a noninvasive method for assessing the presence of electrical instability in the fully conscious animal. Clinical studies will pursue the goals outlined in the grant proposal. Specifically we shall attempt to categorize psychosocial factors in daily life as well as the trigger factors which are associated with the occurrence of malignant arrhythmias. We shall also investigate the role of psychotropic drugs and their effect on ventricular ectopic activity.